Biologic Choice Should Be Guided by Disease Severity Not Malignancy in Patients With Inflammatory Bowel Disease
Authors: Annie Zhou, Ashish Srinivasan, Abhinav Vasudevan
Journal: Clinical Gastroenterology and Hepatology (2023)

We congratulate Holmer et al1Holmer A.K. et al.Clin Gastroenterol Hepatol. 2023; 21: 1598-1606Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar for publishing important data on the impact that biologic choice may have on progression-free and recurrence-free survival in the setting of active and recent malignancy, respectively, in patients with inflammatory bowel disease (IBD). Their data comparing these outcomes, stratified by anti–tumor necrosis factor (TNF) vs non-TNF therapies, indicated that progression-free and recurrence-free survival were not influenced by biologic class. In fact, the data presented by Holmer et al1Holmer A.K. et al.Clin Gastroenterol Hepatol. 2023; 21: 1598-1606Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar should empower clinicians to initiate and continue biologic therapies, including anti-TNF agents, on the basis of patient needs, disease severity, and treatment goals, even in the setting of malignancy. This remains of particular importance in situations such as perianal Crohn's disease, postoperative recurrence, and acute severe colitis, among others, in which data support the use of first-line anti-TNF therapy ahead of non-TNF biologics. Nevertheless, therapeutic decision making in the context of active or recent malignancy is clinically complex, highlighting the value in adopting a cross-disciplinary approach between IBD physicians and oncologists. However, it is important to acknowledge that anti-TNF therapies have been associated previously with higher rates of melanoma and lymphoma, which may impact their initiation and ongoing prescription, in patients with these malignancies.2Gordon H. et al.J Crohns Colitis. 2023; 17: 827-854Crossref PubMed Scopus (47) Google Scholar Age also may have been a factor in prescribing biologics because non-TNF biologics such as vedolizumab and ustekinumab have a more advantageous safety profile in the elderly in relation to malignancy risk and serious infections. Hence, it would be interesting to know whether biologic prescription was influenced by the malignancy type and patient characteristics in the current study because Holmer et al1Holmer A.K. et al.Clin Gastroenterol Hepatol. 2023; 21: 1598-1606Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar have shown comparable outcomes between anti-TNF and non-TNF biologics. Nevertheless, it remains important to highlight that anti-TNF therapies such as infliximab have shown success as rescue therapy in steroid-refractory immune checkpoint inhibitor (ICI)-induced colitis, including in the setting of metastatic melanoma.3Dougan M. et al.Gastroenterology. 2021; 160: 1384-1393Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar More recently, data pertaining to the efficacy and safety of non-TNF biologics such as vedolizumab for treatment of ICI-induced colitis also has been published,4Zou F. et al.J Immunother Cancer. 2021; 9e003277Google Scholar with data regarding the potential of ustekinumab in this context also emerging.5Thomas A.S. et al.N Engl J Med. 2021; 384: 581-583Crossref PubMed Scopus (57) Google Scholar In light of this, parallels may be drawn between the use of biologics in the treatment of ICI-induced colitis, and the use of biologic therapies in IBD patients with an active or recent history of malignancy. This was supported by a recent study by Badran et al6Badran Y.R. et al.J Immunother Cancer. 2023; 11e007195Crossref PubMed Scopus (2) Google Scholar that documented comparable progression-free survival after recommencement of immunotherapy after infliximab or vedolizumab therapy for ICI-induced colitis. However, it is important to acknowledge that the majority of patients who require biologic rescue therapy for ICI-induced colitis do not require ongoing maintenance biologic therapy; representing an important point of distinction from biologic prescription in patients with IBD. Primary nonresponse and loss of response to biologic therapy is common, reflecting that patients frequently require more than 1 biologic over the duration of their disease.7Srinivasan A. et al.Therap Adv Gastroenterol. 2022; 1517562848211070940Crossref PubMed Scopus (5) Google Scholar In light of this, cumulative duration and sequencing of immunosuppression spanning multiple lines of therapy also may represent an important determinant of progression-free and recurrence-free survival in the setting of active and recent malignancy. We note that Holmer et al1Holmer A.K. et al.Clin Gastroenterol Hepatol. 2023; 21: 1598-1606Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar chose to stratify therapies based on the first biologic prescribed during or immediately after malignancy, rather than the biologic prescribed for the longest duration during cancer therapy. In light of concerns regarding a possible reduction in the efficacy of ICIs when biologics are used to treat immune-related adverse events,8Verheijden R.J. et al.NPJ Precis Oncol. 2023; 7: 41Crossref PubMed Scopus (12) Google Scholar we also would be interested to clarify whether progression-free survival and cancer recurrence differed between patients who remained on maintenance biologic therapy while on concurrent ICI therapy for their malignancy. The study by Holmer et al1Holmer A.K. et al.Clin Gastroenterol Hepatol. 2023; 21: 1598-1606Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar provides important reassurance and preliminary guidance regarding the prescription of biologic therapies, including anti-TNF therapies, in IBD patients with an active or recent history of malignancy. Their conclusion that biologic choice should, within reason, be based on disease severity rather than solely on malignancy history is clinically empowering, and provides some clarity to an area in which patients and clinicians alike are yearning for the same. Nevertheless, larger prospective registry studies that include newer IBD therapies and accommodate a longer duration of follow-up evaluation capable of identifying late recurrence are needed. This may be particularly important in identifying potential long-term advantages associated with gut-specific vs systematic immunosuppression in patients with IBD after malignancy. Overall, the findings of this study support the continued prescription of biologic therapy in the setting of active or recent malignancy with a view toward prioritizing IBD disease control. Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort StudyClinical Gastroenterology and HepatologyVol. 21Issue 6PreviewSafety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. Full-Text PDF